Comparative genomic analysis reveals varying levels of mammalian adaptation to coronavirus infections.

Comparative genomic analysis reveals varying levels of mammalian adaptation to coronavirus infections.
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DOI:
10.1371/journal.pcbi.1009560
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发表时间:
2021-11
影响因子:
4.3
通讯作者:
Singh M
Singh M
中科院分区:
生物学2区
文献类型:
--
作者:
King SB;Singh M

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严重急性呼吸道冠状病毒 2 (SARS-CoV-2) 是 COVID-19 的病原体,具有人畜共患来源。评估与感染现代动物宿主祖先物种的 SARS-CoV-2 类似的冠状病毒是否可用于识别潜在危险冠状病毒的其他储存库的进化分析。我们推断,如果一个物种的进化枝反复暴露于病毒,那么它们与病毒进入相关的蛋白质可能会表现出影响宿主敏感性或反应的适应性。我们对血管紧张素转换酶 2 (ACE2)(SARS-CoV-2 的细胞受体)的哺乳动物系统发育进行了比较分析,以便发现作用于其与 SARS-CoV-2 刺突蛋白结合界面的选择的证据。我们发现,在啮齿类动物中,有证据表明在构成 ACE2-刺突相互作用界面的位置处存在适应性氨基酸取代,而灵长类动物和其他一些哺乳动物分支中 ACE2 蛋白内的变异与进化适应不一致。我们还分析了氨肽酶 N (APN),它是人类冠状病毒 229E(一种引起普通感冒的病毒)的受体,并找到了灵长类动物适应的证据。总而言之,我们的结果表明,啮齿类动物和灵长类动物谱系可能在古代就分别接触过类似于 SARS-CoV-2 和 HCoV-229E 的病毒。 SARS样冠状病毒,如SARS-CoV和SARS-CoV-2,是一类对人类健康构成重大威胁的病原体。在整个动物王国中,我们发现这些类型的病毒引起的症状严重程度存在很大差异。此前的研究表明,已知的病毒载体(如中华马蹄蝠)对类 SARS 病毒具有适应性。发现其他宿主蛋白质对类似 SARS 病毒感染的适应证据,将有助于了解是否有其他哺乳动物进化枝之前曾接触过这些病毒。在我们的研究中,我们描述了 SARS 样病毒的哺乳动物宿主受体 ACE2 在广泛的哺乳动物系统发育中的进化。我们的比较基因组见解揭示了啮齿类动物进化枝内 ACE2/病毒结合界面的快速进化模式,而在灵长类动物或尚未已知为 SARS 宿主的其他哺乳动物中几乎没有发现适应性。这些结果表明,一些啮齿类动物可能已经获得了某种形式的对类SARS冠状病毒感染的耐受性或抵抗力,而未适应的哺乳动物和灵长类动物可能更容易受到症状性疾病的影响。
Severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is of zoonotic origin. Evolutionary analyses assessing whether coronaviruses similar to SARS-CoV-2 infected ancestral species of modern-day animal hosts could be useful in identifying additional reservoirs of potentially dangerous coronaviruses. We reasoned that if a clade of species has been repeatedly exposed to a virus, then their proteins relevant for viral entry may exhibit adaptations that affect host susceptibility or response. We perform comparative analyses across the mammalian phylogeny of angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2, in order to uncover evidence for selection acting at its binding interface with the SARS-CoV-2 spike protein. We uncover that in rodents there is evidence for adaptive amino acid substitutions at positions comprising the ACE2-spike interaction interface, whereas the variation within ACE2 proteins in primates and some other mammalian clades is not consistent with evolutionary adaptations. We also analyze aminopeptidase N (APN), the receptor for the human coronavirus 229E, a virus that causes the common cold, and find evidence for adaptation in primates. Altogether, our results suggest that the rodent and primate lineages may have had ancient exposures to viruses similar to SARS-CoV-2 and HCoV-229E, respectively. SARS-like coronaviruses, such as SARS-CoV and SARS-CoV-2, are a class of pathogens that have been a significant threat to human health. Across the animal kingdom, we see considerable differences in the severity of symptoms caused by these types of viruses. Previous research has shown adaptations to SARS-like viruses in known viral vectors such as Chinese Horseshoe bats. Uncovering evidence of adaptations to SARS-like viral infections in proteins of other hosts would shed light on whether additional mammalian clades have been previously exposed to these viruses. In our study, we characterize the evolution of the mammalian host receptor of SARS-like viruses, ACE2, across a broad mammalian phylogeny. Our comparative genomic insights reveal a pattern of rapid evolution of the ACE2/virus binding interface within the rodent clade, while finding little adaptation within primates or among other mammals not already known to be SARS hosts. These results suggest that some rodent species may have acquired some form of tolerance or resistance to infections from SARS-like coronaviruses, while non-adapted mammals and primates may be more susceptible to symptomatic disease.
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发表时间: 2020-09-21
影响因子: 7.4
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发表时间: 2016-08
期刊: Nature reviews. Microbiology
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发表时间: 2007-10
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发表时间: 2020-09-04
期刊: Science (New York, N.Y.)
影响因子: --
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